Su un graffito de Ekron

The article consists in a new interpretation of a short inscription engraved before firing on a store amphora fragment found at Tell Miqneh/Eqron in a VIIth century B.C. temple context. It is supposed that both the names quoted are personal namesL’articolo consiste in una nuova ipotesi di interpretazione di una breve iscrizione incisa prima della cottura su un frammento di anfora commerciale trovata a Tell Miqneh/Ekron in un contesto templare di VII secolo a.C. Si suppone che ambedue i nomi presenti sul coccio siano nomi propri di person

Handbook of Territorial and Local Development Strategies

All places are important to the future wellbeing of Europe. The European Union (EU) is committed to ensuring that the development potential of places is uncovered and valorised. Integrated territorial and local develop- ment strategies promoted by EU cohesion policy are relevant tools to sustain this process. The ‘Handbook of Territorial and Local Development Strategies’ provides valuable knowledge on how to design and implement integrated strategies in areas other than urban areas. It aims to serve managing authorities of operational programmes, local strategy owners as well as other stakeholders involved in the process. The Handbook is a joint initiative by the European Commission’s Directorates-General for Regional and Urban Policy (DG REGIO) and the Joint Research Centre (JRC), and it benefits from the active contribution of policy-makers, practitioners and scholars

Inhibition of glucose-6-phosphate dehydrogenase sensitizes cisplatin-resistant cells to death.

The mechanisms of cisplatin resistance, one of the major limitations of current chemotherapy, has only partially been described. We previously demonstrated that cisplatin-resistant ovarian cancer cells (C13), are characterized by reduced mitochondrial activity and higher glucose-dependency when compared to the cisplatin-sensitive counterpart (2008). In this work we further characterized the role of metabolic transformation in cisplatin resistance. By using transmitochondrial hybrids we show that metabolic reprogramming of cisplatin-resistant cell is not caused by inherent mtDNA mutations. We also found that C13 cells not only present an increased glucose-uptake and consumption, but also exhibit increased expression and enzymatic activity of the Pentose Phosphate pathway (PPP) enzyme Glucose-6-Phosphate Dehydrogenase (G6PDH). Moreover, we show that cisplatin-resistant cells are more sensitive to G6PDH inhibition. Even if the metabolomic fingerprint of ovarian cancer cells remains to be further elucidated, these findings indicate that PPP offers innovative potential targets to overcome cisplatin resistance.This work was financially supported by PRAT (University of Padova), grant no. CPDA124517/12 and MIUR grant no 60A04–0443. DC fellowship was supported by grant no. CPDR134012. AR was supported by the AIRC grant no. IG 15863 and by the University of Padova grant no. CPDA 123598.This is the final version of the article. It first appeared from Impact Journals via http://dx.doi.org/10.18632/oncotarget.494

Metabolic reprogramming identifies the most aggressive lesions at early phases of hepatic carcinogenesis

Metabolic changes are associated with cancer, but whether they are just bystander effects of deregulated oncogenic signaling pathways or characterize early phases of tumorigenesis remains unclear. Here we show in a rat model of hepatocarcinogenesis that early preneoplastic foci and nodules that progress towards hepatocellular carcinoma (HCC) are characterized both by inhibition of oxidative phosphorylation (OXPHOS) and by enhanced glucose utilization to fuel the pentose phosphate pathway (PPP). These changes respectively require increased expression of the mitochondrial chaperone TRAP1 and of the transcription factor NRF2 that induces the expression of the rate-limiting PPP enzyme glucose-6-phosphate dehydrogenase (G6PD), following miR-1 inhibition. Such metabolic rewiring exclusively identifies a subset of aggressive cytokeratin-19 positive preneoplastic hepatocytes and not slowly growing lesions. No such metabolic changes were observed during non-neoplastic liver regeneration occurring after two/third partial hepatectomy. TRAP1 silencing inhibited the colony forming ability of HCC cells while NRF2 silencing decreased G6PD expression and concomitantly increased miR-1; conversely, transfection with miR-1 mimic abolished G6PD expression. Finally, in human HCC patients increased G6PD expression levels correlates with grading, metastasis and poor prognosis. Our results demonstrate that the metabolic deregulation orchestrated by TRAP1 and NRF2 is an early event restricted to the more aggressive preneoplastic lesions

High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections

The mitochondrial chaperone TRAP1 promotes neoplastic growth by inhibiting succinate dehydrogenase

Cancer is a highly heterogeneous and complex disease, whose development requires a reorganization of cell metabolism. Most tumor cells downregulate mitochondrial oxidative phosphorylation and increase the rate of glucose consumption and lactate release, independently of oxygen availability (the Warburg effect). This metabolic rewiring is believed to favour tumor growth and survival. However the molecular mechanisms that inhibit oxidative phosphorylation (OXPHOS) during neoplastic progression are only partially understood. Within this context, we studied TRAP1, a conserved chaperone of the Heat Shock Protein 90 (HSP90) family, localized mainly in the mitochondrial matrix and whose expression is induced in the majority of tumor types. We found that TRAP1 is associated to succinate dehydrogenase (SDH), the Complex II of the respiratory chain. We observed in different tumor cell models that TRAP1 diminished in vivo tumor cell respiration by inhibiting the succinate:coenzyme Q reductase (SQR) activity of Complex II. This Complex II inhibition was further enhanced in TRAP1-expressing cells that progressed through a focus forming assay (in vitro tumorigenesis assay), causing an accumulation of succinate that led to the stabilization of the pro-neoplastic transcription factor HIF1alpha thus favouring the metabolic switch necessary for tumor growth and progression. In fact, we observe in vitro e in vivo tumorigenesis only in TRAP1 expressing cellsIl cancro è una malattia altamente complessa ed eterogenea, il cui sviluppo richiede una riorganizzazione del metabolismo cellulare. La maggior parte delle cellule tumorali diminuisce la fosforilazione ossidativa mitocondriale e aumenta invece la quantità di glucosio consumato e di produzione di lattato, in maniera completamente indipendente dalla disponibilità di ossigeno. Questo fenomeno è noto come Effetto Warburg. Si pensa che questa riprogrammazione metabolica favorisca la crescita e la sopravvivenza del tumore. Comunque sono solo parzialmente noti i meccanismi molecolari che inibiscono la fosforilazione ossidativa (OXPHOS) durante la trasformazione neoplastica. In questo contesto, abbiamo deciso di studiare TRAP1, uno sciaperone appartenente alla famiglia delle Heat Shock Protein 90 (HSP90), che si trova principalmente nella matrice mitocondriale e la cui espressione è indotta nella maggior parte dei tumori. I risultati che abbiamo ottenuto mostrano l’associazione di TRAP1 alla succinato deidrogenasi (SDH), il Complesso II della catena respiratoria. Abbiamo osservato in diversi modelli cellulari tumorali che TRAP1 diminuisce la respirazione delle cellule tumorali in vivo inibendo l’attività succinato:coenzima Q reduttasi (SQR) del Complesso II. L’inibizione del Complesso II aumenta ulteriormente nelle cellule esprimenti TRAP1 durante il saggio di tumorigenesi in vitro, provocando l’accumulo di succinato. Questo aumento di succinato induce la stabilizzazione del fattore di trascrizione pro-neoplastico HIF1alpha favorendo lo switch metabolico necessario per la crescita e la progressione tumorale. Infatti, si osserva tumorigenesi in vitro e in vivo solo nelle cellule esprimenti TRAP1

Studio di HIPK1: localizzazione cellulare e funzione

studio di HIPK1, una protein chinasi implicata nel processo tumorale. Si vuole studiare la sua localizzazione citoplasmatica e nucleare

La competenza grammaticale nelle Prove INVALSI

Il presente contributo vuole indagare il modo in cui viene concepita la competenza grammaticale nelle Prove INVALSI di Italiano. La grammatica ancora oggi nella prassi didattica risulta fortemente ancorata a una didattica tradizionale, configurandosi come l’anello debole dell’educazione linguistica, mentre la valutazione di sistema proposta dall’INVALSI muove verso un rinnovamento dell’approccio alla disciplina. Il contributo intende indagare la politica linguistica sottostante alle Prove, prendendo in analisi alcuni quesiti grammaticali delle Prove INVALSI della classe V della scuola primaria al fine di esplicitare la prospettiva linguistica sottesa, alla luce delle dichiarazioni presenti nei documenti normativi (Indicazioni Nazionali per il curricolo e Quadro di Riferimento delle Prove INVALSI di Italiano). Si compareranno i presupposti presentati dai documenti per comprendere l’evoluzione della politica linguistica nella più ampia considerazione della politica scolastica general

Gli Aramei e l’alfabeto

L’article vise à reconstruire le processus d’adoption, par les nouveaux états araméens, de l’alphabet à 22 consonnes et son développement au cours du temps. Une attention particulière est accordée à la première période de l’adoption, avec une tentative pour différencier plusieurs sources et moments de pénétration en Syrie de l’écriture alphabétique : une première adoption en Syrie du Nord-Est (Gozana) d’un type d’écriture bientôt abandonné, et la pénétration successive dans les états plus occidentaux d’un type différent, qui va prévaloir et se développer rapidement.The paper aims to reconstruct the adoption of the alphabet of 22 consonants by the Aramaeans and its development during the time. Special attention is given to the early moments of the adoption with the proposal of different sources and periods: a first adoption in North-Eastern Syria (Gozana), with a kind of script soon abandoned, and a later one in the Western territories, which prevailed and which developed quickly